Unicentric Castleman Disease: Symptoms, Diagnosis, and Treatment Options

Introduction

Castleman disease is a rare condition that affects the lymph nodes and related tissues. First identified by Dr. Benjamin Castleman in the 1950s, it has two primary forms: unicentric and multicentric. Unicentric Castleman disease (UCD) is the more common and less severe type, typically involving a single lymph node or a group of lymph nodes in one area of the body. This article provides a thorough overview of UCD, including risk factors, symptoms, diagnostic tests, treatment options, and home care strategies. Understanding these aspects can empower patients to make informed decisions about their health.

Definition of Unicentric Castleman Disease

Unicentric Castleman disease (UCD) is a rare disorder that affects a single lymph node or a group of lymph nodes in one localized area. This article will delve into the risk factors, symptoms, diagnostic tests, medications, procedures, and home care strategies for managing UCD.

Description of Unicentric Castleman Disease

Unicentric Castleman disease (UCD) involves abnormal growth of lymphatic tissue, typically confined to one region. The lymphatic system, a key part of the immune system, includes lymph nodes that filter harmful substances. In UCD, a single lymph node or a group of lymph nodes enlarges due to cell overgrowth, which can exert pressure on nearby organs and tissues, leading to discomfort or other symptoms.

Unlike multicentric Castleman disease, which affects multiple lymph nodes and causes more severe, systemic symptoms, UCD is usually localized and less aggressive. Most patients with UCD do not experience widespread symptoms, and the condition is often discovered incidentally during imaging tests for unrelated issues.

UCD is rare, with only a few thousand cases diagnosed worldwide each year. It can affect individuals of any age but is more commonly diagnosed in adults. The exact cause of UCD remains unclear, though it may involve abnormal immune system activity. Early diagnosis and treatment are essential to prevent complications, such as compression of nearby organs or tissues.

Risk Factors for Developing Unicentric Castleman Disease

Lifestyle Risk Factors

No specific lifestyle factors have been directly linked to an increased risk of developing unicentric Castleman disease. Unlike many other conditions, UCD does not appear to be influenced by diet, exercise, smoking, or alcohol consumption. However, maintaining a healthy lifestyle supports overall immune function and well-being. While lifestyle changes may not prevent UCD, they can aid in recovery and symptom management.

Medical Risk Factors

Certain medical conditions may increase the likelihood of developing UCD. Individuals with weakened immune systems, whether due to chronic illness or immune-suppressing medications, may be at slightly higher risk. Additionally, viral infections like human herpesvirus 8 (HHV-8) are associated with multicentric Castleman disease, though their role in UCD is less clear. Discussing your medical history with a healthcare provider can help assess your risk of developing UCD.

Genetic and Age-Related Risk Factors

While UCD can affect people of all ages, it is more commonly diagnosed in adults, particularly those aged 30 to 50. There is no strong evidence to suggest that UCD is inherited. However, researchers are investigating potential genetic factors that may contribute to the disease. Age-related changes in the immune system may also play a role, as the immune system becomes less efficient with age, potentially leading to abnormal cell growth in the lymphatic system.

Clinical Manifestations of Unicentric Castleman Disease

Fever

Fever occurs in 30-40% of UCD patients. It is the body’s response to inflammation or infection, often triggered by the overproduction of inflammatory proteins called cytokines. These cytokines are released by the abnormal lymph node tissue, leading to systemic symptoms like fever. Patients may experience intermittent or persistent fevers, which can range from mild to high-grade. Fever is often an early sign of UCD but can also develop later, especially if the lymph node mass is large or pressing on nearby structures.

Fatigue

Fatigue is reported in 50-60% of UCD patients. It is often related to the immune response to abnormal lymph node growth. The overproduction of cytokines can lead to chronic inflammation, draining the body’s energy reserves. If UCD causes anemia, this can further contribute to fatigue. Fatigue in UCD can be persistent and debilitating, affecting daily activities and overall quality of life.

Weight Loss

Weight loss is seen in 20-30% of UCD patients. Chronic inflammation increases the body’s metabolic demands, leading to gradual weight loss. The overproduction of cytokines can suppress appetite and increase the breakdown of muscle and fat tissue. Weight loss may be accompanied by other systemic symptoms like fever and night sweats. In some cases, significant weight loss can lead to malnutrition if not addressed.

Night Sweats

Night sweats occur in 30-40% of UCD patients. These episodes of excessive sweating during sleep often drench bedclothes and sheets. Night sweats are caused by the body’s inflammatory response to abnormal lymph node tissue, leading to fluctuations in body temperature. Like fever, night sweats are driven by cytokine release and can disrupt sleep, contributing to fatigue.

Lymphadenopathy

Lymphadenopathy, or swollen lymph nodes, is the hallmark feature of UCD, occurring in 100% of cases. The abnormal growth is typically localized to a single lymph node or a group of lymph nodes in one region. The affected lymph node may be painless or tender, with size varying from small to very large. Lymphadenopathy in UCD is caused by lymphoid tissue overgrowth, which can compress nearby structures, causing pain or discomfort.

Abdominal Pain

Abdominal pain is reported in 20-30% of UCD patients, particularly when the affected lymph node is in the abdomen. The enlarged lymph node can press on surrounding organs, such as the intestines or stomach, causing discomfort or pain. In some cases, the mass may obstruct the normal flow of digestive contents, leading to bloating, nausea, or vomiting. Abdominal pain in UCD is often dull and persistent but can become sharp if the lymph node grows rapidly.

Anemia

Anemia is present in 30-40% of UCD patients. It occurs when there is a decrease in red blood cells or hemoglobin, which carry oxygen throughout the body. In UCD, anemia is often caused by chronic inflammation, which interferes with red blood cell production. Symptoms of anemia include fatigue, weakness, shortness of breath, and pale skin. Anemia can also worsen other symptoms, such as fatigue and dizziness.

Hyperhidrosis

Hyperhidrosis, or excessive sweating, affects 20-30% of UCD patients. This symptom is closely related to night sweats but can occur during the day as well. Hyperhidrosis is caused by the body’s inflammatory response and cytokine release, which affect temperature regulation. Patients may experience sweating unrelated to physical activity or external temperature, leading to discomfort and social embarrassment.

Skin Rash

Skin rash occurs in 10-15% of UCD patients. It may appear as red, raised patches and is often associated with the immune response to abnormal lymph node tissue. In some cases, the rash may be itchy or painful. Skin rashes in UCD are thought to result from cytokine overproduction, which causes skin inflammation.

Hepatomegaly

Hepatomegaly, or an enlarged liver, is seen in 10-20% of UCD patients. It occurs when abnormal lymph node growth causes inflammation that spreads to the liver, leading to its enlargement. Hepatomegaly can cause discomfort or pain in the upper right abdomen and may be associated with symptoms like jaundice (yellowing of the skin and eyes) or fatigue. In some cases, hepatomegaly is detected during imaging studies or physical exams before noticeable symptoms arise.

Diagnostic Evaluation of Unicentric Castleman Disease

The diagnosis of unicentric Castleman disease (UCD) involves clinical evaluation, imaging studies, and laboratory tests. Since UCD often presents with nonspecific symptoms like fever, fatigue, and lymphadenopathy, it is important to rule out other conditions, such as infections, autoimmune diseases, and cancers like lymphoma. The diagnostic process typically begins with a medical history and physical examination, followed by imaging studies to identify the location and size of the affected lymph node. A biopsy is usually required to confirm the diagnosis, as it allows for tissue examination under a microscope. Additional tests, such as blood tests and serological studies, may be performed to assess overall health and rule out other conditions.

CT Scan

A computed tomography (CT) scan uses X-rays to create detailed cross-sectional images of the body. During the test, the patient lies on a table that slides into a large, doughnut-shaped machine. The machine takes multiple X-ray images from different angles, which are combined by a computer to create a detailed picture of the body’s interior. CT scans are particularly useful for identifying enlarged lymph nodes and determining their size, shape, and location. In UCD, a CT scan can help pinpoint the affected lymph node and assess whether it is pressing on nearby structures, such as blood vessels or organs.

Results indicating UCD on a CT scan typically show a single, enlarged lymph node or a group of lymph nodes in one region. The lymph node may appear as a well-defined mass with smooth or irregular borders. In some cases, the lymph node may show signs of calcification (calcium deposits) or necrosis (tissue death), helping differentiate UCD from other conditions like lymphoma. If the CT scan does not show any enlarged lymph nodes, it is unlikely the patient has UCD, and other causes of symptoms should be investigated.

MRI

Magnetic resonance imaging (MRI) uses powerful magnets and radio waves to create detailed images of the body’s internal structures. Unlike CT scans, MRI does not use radiation, making it safer for certain patients, such as pregnant women. During the test, the patient lies on a table that slides into a large, tube-shaped machine. The machine generates a magnetic field, causing the body’s atoms to emit signals captured by a computer to create images. MRI is particularly useful for evaluating soft tissues, such as lymph nodes, and can provide more detailed information about the structure and composition of the affected lymph node in UCD.

Results indicating UCD on an MRI typically show a single, enlarged lymph node with specific characteristics, such as a homogeneous (uniform) appearance or areas of necrosis. The MRI may also reveal whether the lymph node is compressing nearby structures, such as blood vessels or nerves. If the MRI does not show any abnormalities, it is unlikely the patient has UCD, and further testing may be needed to explore other potential causes of symptoms.

Biopsy

A biopsy involves removing a small tissue sample from the affected lymph node for examination under a microscope. This is the most definitive test for diagnosing UCD, as it allows pathologists to observe cellular changes characteristic of the disease. Several types of biopsies exist, including fine-needle aspiration (FNA), core needle biopsy, and excisional biopsy. In most UCD cases, an excisional biopsy, where the entire lymph node is removed, is preferred for the most comprehensive information.

Results indicating UCD on a biopsy typically show abnormal lymphoid tissue with features like enlarged follicles (structures that produce immune cells) and increased blood vessels. The tissue may also show signs of inflammation and fibrosis (scarring). If the biopsy does not show these characteristic changes, it is unlikely the patient has UCD, and other conditions, such as lymphoma or infection, should be considered. If biopsy results are inconclusive, additional tests, such as immunohistochemistry or genetic testing, may be needed to confirm the diagnosis.

Blood Tests

Blood tests are often part of the diagnostic evaluation for UCD to assess overall health and rule out other conditions. Common blood tests include a complete blood count (CBC), which measures levels of different blood cell types, and tests for inflammatory markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). These tests can help identify signs of inflammation, anemia, or other abnormalities associated with UCD.

Results indicating UCD on blood tests may show elevated levels of inflammatory markers, such as CRP and ESR, suggesting chronic inflammation. Anemia may also be present, indicated by low levels of red blood cells or hemoglobin. If blood tests do not show abnormalities, it is less likely the patient has UCD, and other potential causes of symptoms should be explored. However, normal blood test results do not completely rule out UCD, as some patients may have normal blood work despite having the disease.

Ultrasound

Ultrasound is a non-invasive imaging test that uses sound waves to create images of internal structures. During the test, a handheld device called a transducer is placed on the skin, and sound waves are sent into the body. The sound waves bounce off tissues and organs, creating echoes that are captured by the transducer and used to generate images. Ultrasound is often used to evaluate lymph nodes in areas like the neck, abdomen, or groin and can help determine whether a lymph node is enlarged or abnormal.

Results indicating UCD on an ultrasound typically show a single, enlarged lymph node with a well-defined structure. The lymph node may appear as a solid mass with areas of increased blood flow, detectable using Doppler ultrasound. If the ultrasound does not show any enlarged lymph nodes, it is less likely the patient has UCD, and further testing may be needed to investigate other causes of symptoms.

PET Scan

Positron emission tomography (PET) scan uses a small amount of radioactive material to detect areas of increased metabolic activity. During the test, the patient is injected with a radioactive tracer, which is absorbed by actively growing or dividing cells. The PET scanner detects the radiation emitted by the tracer and creates images showing areas of increased activity. PET scans are often used to evaluate lymph nodes and can help differentiate between benign (non-cancerous) and malignant (cancerous) conditions.

Results indicating UCD on a PET scan typically show a single area of increased metabolic activity corresponding to the enlarged lymph node. The level of activity may be lower than what is typically seen in cancers like lymphoma, helping distinguish UCD from other conditions. If the PET scan does not show any areas of increased activity, it is less likely the patient has UCD, and other potential causes of symptoms should be considered.

What if all Tests are Negative but Symptoms Persist?

If all diagnostic tests are negative but symptoms persist, it is important to continue working with your healthcare provider to explore other potential causes. Conditions like infections, autoimmune diseases, and cancers such as lymphoma can present with similar symptoms to UCD and may require additional testing or specialist referrals. In some cases, a repeat biopsy or more advanced imaging studies may be needed to identify the underlying cause. It is crucial to advocate for your health and seek a second opinion if necessary.

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Treatment Options for Unicentric Castleman Disease

Medications for Unicentric Castleman Disease

Surgery

Surgery is the most common treatment for unicentric Castleman disease (UCD), involving the removal of the affected lymph node or mass causing symptoms.

It is typically the first-line treatment, especially when the disease is localized to a single lymph node. Surgery is recommended when the mass is accessible and can be safely removed.

Most patients experience a full recovery after surgery, with symptoms resolving shortly after. In many cases, surgery is curative, meaning no further treatment is required.

Corticosteroids

Corticosteroids help reduce inflammation and suppress the immune system, which can alleviate symptoms and shrink the affected lymph node.

They may be used before surgery to make the lymph node easier to remove or in cases where surgery is not possible due to other health conditions.

Patients often notice symptom improvement within days to weeks. However, long-term use can lead to side effects, so corticosteroids are typically prescribed for short durations.

Rituximab

Rituximab, a monoclonal antibody, targets a specific protein on B cells to reduce their activity in UCD.

It is often used when surgery is not an option or corticosteroids are ineffective. Rituximab may also be considered in more aggressive cases or when there is a risk of relapse.

Patients generally see symptom improvement within weeks. The treatment is usually well-tolerated, though multiple doses may be required for optimal results.

Tocilizumab

Tocilizumab blocks interleukin-6 (IL-6), a protein involved in inflammation, to reduce symptoms in UCD.

It is used when surgery is not feasible or when other treatments, like corticosteroids or rituximab, have not been effective. Tocilizumab may also serve as a long-term treatment option.

Patients often experience symptom relief within a few weeks. While generally well-tolerated, regular monitoring is necessary to ensure its effectiveness.

Siltuximab

Siltuximab, another IL-6 blocker, is approved for multicentric Castleman disease but may be used in some UCD cases.

It is typically reserved for patients who do not respond to other treatments or have more aggressive disease. Siltuximab is administered intravenously, usually every three weeks.

Patients may experience symptom improvement within weeks. Regular monitoring is required to assess its effectiveness, though it is generally well-tolerated.

Chemotherapy

Chemotherapy uses drugs to kill rapidly dividing cells, including immune cells, and is reserved for more aggressive UCD cases or when other treatments fail.

It is often combined with other therapies, such as corticosteroids or rituximab, in severe cases.

While chemotherapy can reduce symptoms, it may cause significant side effects, including fatigue, nausea, and an increased risk of infection.

Immunotherapy

Immunotherapy helps the immune system fight disease and may be used in UCD to enhance the body’s defenses against abnormal lymph node growth.

It is typically considered when other treatments are ineffective or the disease is more aggressive. Immunotherapy may be combined with chemotherapy or corticosteroids.

Symptom improvement varies, and regular monitoring is necessary to evaluate its effectiveness.

Interferon

Interferon, a protein that regulates the immune system, may be used in UCD to reduce immune activity and control symptoms.

It is generally used when other treatments fail or the disease is more aggressive. Interferon is administered via injections over several weeks or months.

Patients may see symptom improvement within weeks, though side effects like flu-like symptoms and fatigue are possible.

Anakinra

Anakinra blocks interleukin-1 (IL-1), a protein involved in inflammation, to reduce symptoms in UCD.

It is typically used when other treatments, such as corticosteroids or rituximab, are ineffective. Anakinra may also be used as a long-term treatment.

Patients often experience symptom relief within weeks. Regular monitoring is required to ensure its effectiveness, though it is generally well-tolerated.

Thalidomide

Thalidomide modulates the immune system and reduces inflammation, helping control symptoms and slow UCD progression.

It is typically used when other treatments fail or the disease is more aggressive. Thalidomide may be combined with corticosteroids or chemotherapy.

While patients may experience symptom improvement over time, thalidomide can cause significant side effects, including nerve damage and an increased risk of blood clots.

Procedures for Unicentric Castleman Disease

Surgical Excision

Surgical excision, the complete removal of the affected lymph node or mass, is the most common and effective treatment for UCD.

It is typically the first-line treatment, especially when the disease is localized to a single lymph node. Surgery is recommended when the mass is accessible and can be safely removed.

Most patients experience a full recovery after surgical excision, with symptoms resolving shortly after the procedure. In many cases, surgery is curative, requiring no further treatment.

Lymph Node Removal

Lymph node removal involves surgically removing one or more lymph nodes to treat UCD when the disease is localized.

It is recommended when the affected lymph node causes symptoms or poses a risk of complications. Lymph node removal may be combined with other treatments, such as corticosteroids or rituximab.

While patients often experience symptom relief, the procedure carries risks, including infection and lymphedema (swelling due to lymph fluid buildup).

Improving Unicentric Castleman Disease and Seeking Medical Help

In addition to medical treatments, several lifestyle changes can improve overall health and well-being while living with unicentric Castleman disease. These include:

1. Balanced diet: A nutritious diet supports your immune system and overall health.
2. Regular exercise: Staying active boosts energy levels and reduces stress.
3. Stress management: Techniques like mindfulness, meditation, or yoga help reduce stress and improve mental well-being.
4. Adequate hydration: Drinking enough water is essential for overall health and helps reduce fatigue.
5. Sleep hygiene: Getting enough rest is crucial for healing and recovery.
6. Avoiding tobacco: Smoking weakens the immune system and increases the risk of complications.
7. Limiting alcohol: Excessive alcohol can interfere with treatment and overall health.
8. Mindfulness practices: Deep breathing and meditation can help manage stress and improve quality of life.
9. Herbal supplements: Some patients find relief with herbal supplements, but always consult your doctor before starting any new supplements.
10. Support groups: Connecting with others who have UCD provides emotional support and practical advice.

Telemedicine offers a convenient way to manage your condition without frequent in-person visits. You can consult with your healthcare provider from home, making it easier to monitor symptoms and adjust your treatment plan. If you experience new or worsening symptoms, seek medical help promptly to prevent complications.

Living with Unicentric Castleman Disease: Tips for Better Quality of Life

Living with unicentric Castleman disease can be challenging, but there are steps you can take to improve your quality of life:

1. Follow your treatment plan as prescribed by your doctor.
2. Maintain a healthy lifestyle, including a balanced diet, regular exercise, and stress management techniques.
3. Stay connected with your healthcare team through telemedicine to monitor your condition and adjust your treatment as needed.
4. Join a support group to connect with others who understand what you’re going through.
5. Take time for self-care, including getting enough rest and managing stress.

Conclusion

Unicentric Castleman disease is a rare condition affecting the lymph nodes, but with proper treatment, most patients can achieve a full recovery. Early diagnosis and treatment are crucial to prevent complications and improve outcomes. If you’re experiencing symptoms or have been diagnosed with UCD, our telemedicine practice is here to help. Schedule a consultation with one of our primary care providers to discuss your treatment options and develop a personalized care plan.

James Kingsley

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